High-throughput Mapping of the Chromatin Structure of Human Promoters

Understanding how chromatin structure affects cellular functions such as transcription and replication in human cells has been limited by a lack of sufficient nucleosome positioning data. We describe a high-resolution microarray approach combined with a novel analysis algorithm to examine the translational nucleosome positions in 3,692 promoters within seven human cell lines. Unlike unexpressed genes without transcription pre-initiation complexes at their promoters, expressed genes or genes containing pre-initiation complexes exhibit characteristic nucleosome-free regions at their transcription start sites. Coupling these data to ChIP-chip analyses reveals that the melanocyte master transcriptional regulator MITF binds predominantly to nucleosome-free regions, supporting the model that nucleosomes limit sequence accessibility. This study thus presents the first global view of human nucleosome positioning and provides a high-throughput tool for analyzing chromatin structure in development and disease. Keywords: Nucleosome positions, MNase digestion, cell type comparison 12 samples in 7 cell types (A375 duplicates, IMR90 triplicates, MALME triplicates, MCF7, T47D, Primary Melanocyte, Mammary Epithelial Cells)